THE THIRTEENTH EIBSEE MEETING ON

October 23-25, 2013

guest speakers: K. Blennow (University of Goteborg) T. Czopka (University of Edinburgh) M. Diamond (Washington University, St. Louis) B. Hyman (Harvard Medical School, Charlestown) DZNE & SyNergy speakers: C. Iadecola (Cornell University, New York) A. Capell, M. Dichgans, D. Dormann, E. Düzel, R. Melki (CNRS, Gif-sur-Yvette) D. Edbauer, S. Fritschi, M. Götz, B. Hemmer, J.C. Morris (Washington University, St. Louis) J. Herms, M. Hipp, G. Höglinger, R. Klein, R.A. Nixon (Langone Medical Center, New York) E. Latz, S. Lichtenthaler, S. Liebscher, R. Ransohoff (Cleveland Clinic) U. Lindauer, E.M. Mandelkow, H. Steiner P. Saftig (University of Kiel) K. Sandhoff (University of Bonn) P. St. George-Hyslop (University of Toronto) J.P. Taylor (St. Jude Children´s Research Hospital, Memphis) H. Wichterle (Columbia University, New York)

organized by: C. Haass (DZNE & SyNergy)

The thirteenth Eibsee Meeting (October 23 - 25, 2013)

"CELLULAR MECHANISMS OF NEURODEGENERATION"

funded by the

DZNE, German Center of Neurodegenerative Diseases - Munich

The Hans und Ilse Breuer Foundation

SyNergy, Munich Cluster for Systems Neurology

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organized by: Christian Haass DZNE, German Center for Neurodegenerative Diseases - Munich, Ludwig-Maximilians-University Munich and SyNergy, Munich Center for Systems Neurology Schillerstr. 44, 80336 Munich

Phone: ++49-89-2180-75471 Fax: ++49-89-2180-75415 e-mail: [email protected] http://www.biochemie.abi.med.uni-muenchen.de/index.html Location

Eibsee Hotel Am Eibsee 1-3 D-82491 Phone: ++49-8821-9881-0 Fax: ++49-8821-82585 Email: [email protected] www.eibsee-hotel.de

The Eibsee Hotel at the foot of the The Eibsee speakers and participants 2010

Travelling by train: take the train to Garmisch (via Munich). In Garmisch please take a taxi to the hotel (about 15-20 min drive). by plane: from Munich airport take the S-Bahn to Munich Central station. At the central station take the train to Garmisch (about 1 hr); from here take a taxi to the hotel. by car: from Munich take the highway to Garmisch. In Garmisch follow the signs to Eibsee. The hotel is at the end of the road right at the foot of the Zugspitze.

Weather It is fall and it may be cold already. For those who like to go on a walk: please bring your hiking boots.

Acknowledgements We greatly appreciate funding of the Eibsee Meeting by the Hans and Ilse Breuer foundation, the German Center for Neurodegenerative Diseases (DZNE) and SyNergy.

PROGRAM

***** Wednesday, October 23 Arrival, Hiking, Opening Lecture

12:30 The traditional “scientific walk” around the lake (if weather permits) 15:00 – 15:15 Welcome (C. Haass) 15:15 – 16:00 Key Note Lecture J.C. Morris, Washington University, St. Louis, USA A new era: DIAN and the secondary prevention of symptomatic Alzheimer´s Disease

16:00 – 16:40 Coffee break

16:40 – 18:10 Seeding, spreading & misfolding Chair: E. Mandelkow Invited speaker 16:40 – 17:05 B. Hyman, Harvard Medical School, Charlestown, USA ApoE as a target for therapies in Alzheimer´s Disease

17:05 – 17:30 R. Melki, Centre National de la Recherche Scientifique (CNRS), Gif-sur-Yvette, France Prion-like propagation of protein assemblies in neurodegenerative diseases

17:30 – 17:55 M. Diamond, Washington University, St. Louis, USA Molecular mechanisms of tau as a prion: implications for diagnosis and therapy Short talk 17:55 – 18:10 M. Hipp, Max Planck Institute of Biochemistry, Munich-Martinsried, Germany Why is protein aggregation toxic to cells?

18:10 – 18:30 Announcement of the Hans & Ilse Breuer Award 2013 (R. Bergfeld/C. Haass)

18:30 Cocktails

19:30 Dinner

Thursday, October 24

9:00 – 10:10 Glio-vascular dysfunction Chair: T. Misgeld Invited speaker 9:00 – 9:25 C. Iadecola, Cornell University, New York, USA Neurovascular regulation in health and disease Short talks 9:25 – 9:40 M. Dichgans, Institute for Stroke and Dementia Research (ISD) & University of Munich, Germany Mechanisms of vascular cognitive impairment

9:40 – 9:55 U. Lindauer, Technical University of Munich, Germany Mechanisms of inverse neurovascular coupling under pathophysiological conditions

9:55 – 10:10 M. Götz, University of Munich, Germany The dynamics of glial cell reaction after brain injury - from heterogeneity to neural stem cell activation

10:10 – 10:50 Coffee Break/Poster Session

10:50 – 11:35 Degeneration, inflammation and demyelination Chair: S. Lichtenthaler Short talks 10:50 – 11:05 E. Latz, DZNE & University of Bonn, Germany Role of NLRP3 in mediating chronic inflammation

11:05 – 11:20 S. Liebscher, Max Planck Institute of Neurobiology & University of Munich, Germany Effects of chronic -secretase inhibition on amyloid plaque – associated synaptic instability in vivo

11:20 – 11:35 T. Czopka, University of Edinburgh, UK Live imaging and genetic manipulation reveal mechanisms of myelinated axon formation in vivo

11:35 – 11:55 Announcement of the Eckhart-Buddecke-Award Chair: C. Haass 11:35 – 11:45 A. Schmidt, Eckhart-Buddecke-Foundation, Münster, Germany Laudatio

11:45 – 11:55 D. Dormann, DZNE & University of Munich, Germany Arginine methylation of FUS – novel insights into the pathomechanisms of FTLD and ALS

12:00 – 13:30 Lunch

13:30 – 14:30 Time for recreation

14:30 – 14:55 Degeneration, inflammation and demyelination (continued) Chair: S. Lichtenthaler Invited speaker 14:30 – 14:55 R. Ransohoff, Cleveland Clinic, Cleveland, USA Neuroinflammation: Echoes of neurodevelopment?

14:55 – 16:25 ALS and FTLD: Genes and mechanisms Chair: B. Schmid Invited speaker 14:55 – 15:20 J.P. Taylor, St. Jude Children´s Research Hospital, Memphis, USA RNA-binding proteins in ALS, FTD and MSP

15:20 – 15:45 H. Wichterle, Columbia University, New York, USA ER stress in a stem cell model of ALS

15:45 – 16:10 P. St. George-Hyslop, University of Toronto, Canada FUSsing with worms Short talks 16:10 – 16:25 D. Edbauer, DZNE Munich, Germany Dipeptide repeat protein pathophysiology in FTLD/ALS with C9orf72 mutation

16:25 – 17:05 Coffee Break/Poster Session

17:05 - 18:25 Lysosomal disorders Chair: J. Herms Invited speaker 17:05 – 17:30 R.A. Nixon, New York University Langone Medical Center, New York, USA Genetic pathways to autophagy disruption in Alzheimer's Disease

17:30 – 17:55 K. Sandhoff, University of Bonn, Germany Mechanisms of neurodegeneration in sphingolipidoses Short talks 17:55 – 18:10 A. Capell, University of Munich, Germany Lysosomal dysfunction in FTLD

18:10 – 18:25 P. Saftig, University of Kiel, Germany Studying lysosomal biology: New insights into neurodegeneration?

19:00 Dinner

Friday, October 25

9:00 – 10:15 Amyloid, aggregation and secretases Chair: M. Dichgans Short talks 9:00 – 9:15 S. Lichtenthaler, DZNE & Technical University of Munich, Germany Function and therapeutic potential of Alzheimer alpha- and beta-secretases

9:15 – 9:30 J. Herms, DZNE Munich, Germany Pharmacological inhibition of BACE1 alters dendritic spine plasticity

9:30 – 9:45 H. Steiner, DZNE & University of Munich, Germany Functional and structural analysis of γ-secretase

9:45 – 10:00 S. Fritschi, DZNE & University of Tübingen, Germany β-Amyloid seeds as therapeutic targets

10:00 – 10:15 E.M. Mandelkow, DZNE Bonn, Germany Aggregation-induced tau pathology in animal models and treatment with aggregation inhibitors

10:15 – 10:55 Coffee Break/Poster Session

10:55 – 12:20 Translational research Chair: U. Lindauer Invited speakers 10:55 – 11:20 K. Blennow, University of Goteborg, Sweden CSF biomarkers for diagnostics, theragnostics and clinical pathogenic studies in Alzheimer´s Disease Short talks 11:20 – 11:35 E. Düzel, DZNE & University of Magdeburg, Germany Imaging function and plasticity of memory circuits in old age

11:35 – 11:50 G. Höglinger, DZNE & Technical University of Munich, Germany Genome-wide siRNA screen identifies modifiers of alpha-synuclein toxicity

11:50 – 12:05 R. Klein, Max Planck Institute of Neurobiology, Munich-Martinsried, Germany Ret rescues mitochondrial complex I deficiency and muscle degeneration of Drosophila Pink1 mutants

12:05 – 12:20 B. Hemmer, Technical University of Munich, Germany The inward rectifying potassium channel KIR 4.1 as an immune target in Multiple Sclerosis

12:30 – 14:00 Lunch

Departure

19:00 Dinner

for participants staying until Saturday, October 26